Previous work has shown that respiratory acidosis causes a decrease in glucose utilization by rat brain, with consumption of endogenous intermediary metabolites and amino acids to maintain normal rates of oxidative phosphorylation. We propose to study these phenomena in developing rat brain. A microwave oven and a freeze-blowing apparatus will be used to achieve rapid cessation of brain metabolism before post- mortem biochemical changes can occur. The rate of brain glucose utilization will be measured by a recently developed method which is based on the "trapping" in brain intermediary metabolites and amino acids of C14 derived from blood (2-C14)-glucose. Intermediary metabolites and amino acids will be assayed in the spectrophotometer using standard enzymatic techniques. There are three objectives of the research. First, we will study brain intermediary metabolism under normal and hypercapnic conditions. Second, we will test the hypothesis that during prolonged hypercapnia there is protein degradation to supply amino acids to maintain respiration. Third, we will investigate the mechanism of the decrease in glucose utilization during hypercapnia by identifying whether it is the change in (H ion) or the change in (CO2) that causes the decrease and by analyzing the earliest metabolite changes during hypercapnia to see if the initial event is an inhibition of phosphofructokinase (as suggested by earlier data). This work is intended to provide the basis for future studies relating temporary alterations in brain intermediary metabolism during development to long term changes in brain function.